Modulation of the Mitochondrial Permeability Transition by Nitric Oxide

Balakirev, Maxim Y.; Khramtsov, Valery V.; Zimmer, Guido

doi:10.1111/j.1432-1033.1997.00710.x

Cited by 105 publications

(62 citation statements)

References 54 publications

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“…31 This NO-induced protective effect may be related to inhibition of mPTP opening concomitant with reperfusion. 32 Thus, the current results suggesting that eNOS plays a role in isoflurane-induced postconditioning may again be related to inhibition of mitochondrial permeability transition through enhanced NO production. Further study will also be required to confirm this intriguing hypothesis.…”

Section: Discussionmentioning

confidence: 69%

Role of Erk1/2, p70s6K, and eNOS in isofluraneinduced cardioprotection during early reperfusionin vivo

Krolikowski

Weihrauch

Bienengraeber

et al. 2006

Can J Anesth/J Can Anesth

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Purpose: Administration of isoflurane during early reperfusion after prolonged coronary artery occlusion decreases myocardial infarct size by activating phosphatidylinositol-3-kinase (PI3K) signal transduction. The extracellular signal-related kinases (Erk1/2) represent a redundant mechanism by which signaling elements downstream from PI3K, including 70-kDA ribosomal protein s6 kinase (p70s6K) and endothelial nitric oxide synthase (eNOS), may be activated to reduce reperfusion injury. We tested the hypothesis Erk1/2, p70s6K, and eNOS mediate isoflurane-induced postconditioning in rabbit myocardium in vivo. Methods: Barbiturate-anesthetized rabbits (n = 78) instrumented for measurement of systemic hemodynamics were subjected to a 30-min coronary occlusion followed by three hours reperfusion. Rabbits were randomly assigned to receive 0.9% saline (control), the Erk1/2 inhibitor PD 098059 (2 mg·kg -1 ), the p70s6K inhibitor rapamycin (0.25 mg·kg -1 ), the nonselective nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine methyl ester (L-NAME; 10 mg·kg -1 ), the selective inducible NOS antagonist aminoguanidine hydrochloride (AG, 300 mg·kg -1 ), or the selective neuronal NOS inhibitor 7-nitroindazole (7-NI, 50 mg·kg -1 ) in the presence or absence of 1.0 minimum alveolar concentration isoflurane administered for three minutes before and two minutes after reperfusion. Results: Brief exposure to 1.0 minimum alveolar concentration isoflurane reduced (P < 0.05) infarct size (21 ± 4% [mean ± SD] of left ventricle area at risk, respectively; triphenyltetrazolium staining) as compared to control (41 ± 5%). PD 098059, rapamycin, and L-NAME, but not AG nor 7-NI, abolished the protection produced by isoflurane. Conclusion:The results suggest that the protective effects of isoflurane against infarction during early reperfusion are mediated by Erk1/2, p70s6K, and eNOS in vivo. Objectif : L'administration d'isoflurane pendant la reperfusion pré-coce qui suit une occlusion prolongée de l'artère coronaire diminue la taille de l'infarctus myocardique en activant la transduction du signal de la phosphatidylinositol-3-kinase (PI3K). Les kinases extracellulaires reliées au signal (Erk1/2) représentent un mécanisme redondant par lequel le signalement des éléments en aval à partir de PI3K, incluant la s6 kinase de protéines ribosomales

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Section: Discussionmentioning

confidence: 69%

Role of Erk1/2, p70s6K, and eNOS in isofluraneinduced cardioprotection during early reperfusionin vivo

Krolikowski

Weihrauch

Bienengraeber

et al. 2006

Can J Anesth/J Can Anesth

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“…Many reports have indicated that high levels of NO induce apoptosis in numerous cell types. Apoptosis appears to be mediated largely by an effect of peroxynitrite on mitochondrial permeability either directly 66,67 or through DNA damage with subsequent activation of the PARS pathway. 68,69 Through the mitochondrial permeability transition, cytochrome C is released, which is a signal for apoptosis.…”

Section: No In Apoptosismentioning

confidence: 99%

Nitric oxide in liver injury

1999

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“…19). Finally, it has been reported that NO can either stimulate or inhibit the MPT in liver mitochondria, often depending upon experimental conditions and the source of mitochondria (23,24).…”

mentioning

confidence: 99%

Nitric Oxide Ameliorates Hydrophobic Bile Acid-induced Apoptosis in Isolated Rat Hepatocytes by Non-mitochondrial Pathways

Gumpricht

Dahl

Yerushalmi

et al. 2002

Journal of Biological Chemistry

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Hydrophobic bile acids are toxic to isolated rat hepatocytes by mechanisms involving mitochondrial dysfunction and oxidative stress. In the current study we examined the role of nitric oxide (NO), a potential mediator of apoptosis, during bile acid-induced apoptosis. Freshly isolated rat hepatocytes and hepatic mitochondria generated NO and peroxynitrite (ONOO ؊ ) in a concentration-and time-dependent manner when exposed to the toxic bile salt glycochenodeoxycholate (GCDC) (25-500 M), which was prevented by the nitric-oxide synthase (NOS) inhibitors N G -monomethyl-N-arginine monoacetate (L-NMMA) and 1400W. Relationships between hepatocyte NO production and apoptosis were examined by comparing the effects of NOS inhibitors with other inhibitors of GCDC-induced apoptosis. Inhibitors of caspases 8 and 9, the mitochondrial permeability transition blocker cyclosporin A, and the antioxidant idebenone reduced NO generation and apoptosis in GCDC-treated hepatocytes. In contrast, NOS inhibitors had no effect on GCDC-induced apoptosis despite marked reduction of NO and ONOO ؊ . However, treatment with the NO donors S-nitroso-N-acetylpenicillamine and spermine NONOate [N-(-aminoethyl)N-(2-hydroxy-2-nitrohydrazino)-1,2-ethylenediamine) inhibited apoptosis and caspase 3 activity while significantly elevating NO levels above GCDC-stimulated levels. Neither NO donors nor NOS inhibitors affected GCDC-induced mitochondrial permeability transition or cytochrome c release from liver mitochondria or GCDC-induced mitochondrial depolarization from isolated hepatocytes, suggesting that NO inhibits bile acid-induced hepatocyte apoptosis by a non-mitochondrial-dependent pathway. In conclusion, whereas NO produced from GCDCtreated hepatocytes neither mediates nor protects against bile acid-induced apoptosis, higher levels of NO inhibit GCDC-induced hepatocyte apoptosis by caspasedependent pathways.

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Modulation of the Mitochondrial Permeability Transition by Nitric Oxide

Cited by 105 publications

References 54 publications

Role of Erk1/2, p70s6K, and eNOS in isofluraneinduced cardioprotection during early reperfusionin vivo

Role of Erk1/2, p70s6K, and eNOS in isofluraneinduced cardioprotection during early reperfusionin vivo

Nitric oxide in liver injury

Nitric Oxide Ameliorates Hydrophobic Bile Acid-induced Apoptosis in Isolated Rat Hepatocytes by Non-mitochondrial Pathways

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